Chronic therapy with chlorpromazine (CPZ) is associated with development of antinuclear antibodies, an IgM-lupus anticoagulant and polyclonal elevation of IgM. These autoantibodies (AAB) are more prevalent in genetically susceptible individuals as suggested by the high frequency of the HLA antigen BW44 in patients with AAB. Preliminary studies indicate that the severity of tardive dyskinesia is increased among patients with HLA-BW44 and AAB. Also, these abnormalities persist after discontinuation of CPZ when therapy is followed by other phenothiazines. In this study we propose to investigate (1) humoral, cellular and genetic abnormalities associated with the production of autoantibodies and (2) the clinical relevance of these findings to the psychiatric population exposed to CPZ. To this effect we plan to evaluate 2 groups of patients with well defined diagnosis of schizophrenia and schizoaffective disorders, one treated with CPZ and the other with neuroleptic agents other than phenothiazines. The last group will serve as control. The two groups will be tissue typed and studied for the presence of autoantibodies to nuclear material (ANA), phospholipids (lupus anticogulant), neuronal tissue (antineuronal antibodies), anti T cell antibodies and lymphocyte subsets. Their peripheral T cell subset profile will be studied with monoclonal antibodies against peripheral T lymphocyte surface antigens. The findings will be correlated with the presence of impairment in cognitive functions and movement disorders as determined by the Wechsler Scale and AIMS score, respectively. We postulate that there is a genetic predisposition to the production of CPZ induced autoantibodies regulated by the HLA marker BW44. This marker is associated with the production of autoantibodies against a regulatory T lymphocyte subset with subsequent alteration of immune homeostasis, B cell hyper-reactivity and enhanced production of autoantibodies. These autoantibodies may cross-react with nuclear material, membrane phospholipids and neuronal tissue modulating the severity of tardive dyskinesia.